This proposal is for the purchase of a state of the art transmission electron microscope with scanning and x-ray microanalytical capabilities to accomplish not only freeze-dried but freeze-hydrated x-ray microanalysis. The instrument will have the following capabilities: 1) high resolution transmission image with a guaranteed resolution of 2 A; 2) low magnification transmission image (down to 50 times); 3) eucentric goniometer stage for specimen tilting; 4) dry pumped differential vacuum system utilizing sputter ion and turbomolecular pumps; 5) high resolution scanning image observation device with 30 A resolution guaranteed; 6) Gatan-cryo section transfer stage for freeze-hydrated section viewing; and (7) a complete x-ray microanalysis system. The instrument will be utilized primarily by a major group of users in the Departments of Pathology, but also members of Medicine, Anesthesiology, and Physiology from the University of Texas Medical School at Houston. Other available time on the instrument could be utilized by additional investigators (with preference given to NIH grant holders) as deemed appropriate by the internal advisory committee. The instrument will be housed in the Electron Microscope Laboratory of the Department of Pathology and Laboratory Medicine. The Department of Pathology and Laboratory Medicine will pay the costs associated with room renovations, installation of the instrument, initial service and personnel costs. After the initial period of installation and break-in and only after each type of activity is validated, users will be charged a nominal hourly fee for the ongoing (but not the installation) costs as is done presently with other shared instruments in the department.